Promoter nucleosome dynamics regulated by signaling through the CTD code

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand  Is a corresponding author
  1. University of Namur, Belgium
  2. LSU Health Sciences Center, United States
  3. Universidad de Salamanca, Spain
  4. Universitat Pompeu Fabra, Spain

Abstract

The phosphorylation of the RNA polymerase II CTD plays a key role in delineating transcribed regions within chromatin by recruiting histone methylases and deacetylases. Using genome-wide nucleosome mapping, we show that CTD S2 phosphorylation controls nucleosome dynamics in the promoter of a subset of 324 genes, including the regulators of cell differentiation ste11 and metabolic adaptation inv1. Mechanistic studies on these genes indicate that during gene activation a local increase of phosphoS2 CTD nearby the promoter impairs the phosphoS5 CTD dependent recruitment of Set1 and the subsequent recruitment of specific HDACs, which leads to nucleosome depletion and efficient transcription. The early increase of phosphoS2 results from the phosphorylation of the CTD S2 kinase Lsk1 by MAP kinase in response to cellular signaling. The artificial tethering of the Lsk1 kinase at the ste11 promoter is sufficient to activate transcription. Therefore, signaling through the CTD code regulates promoter nucleosomes dynamics.

Article and author information

Author details

  1. Philippe Materne

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  2. Jayamani Anandhakumar

    Department of Biochemistry and Molecular Biology, LSU Health Sciences Center, Shreveport, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Valerie Migeot

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  4. Ignacio Soriano

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Carlo Yague-Sanz

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  6. Elena Hidalgo

    Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. Carole Mignion

    Namur Research College, University of Namur, Namur, Belgium
    Competing interests
    The authors declare that no competing interests exist.
  8. Luis Quintales

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  9. Francisco Antequera

    Instituto de Biología Funcional y Genómica, Consejo Superior de Investigaciones Científicas, Universidad de Salamanca, Salamanca, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Damien Hermand

    Namur Research College, University of Namur, Namur, Belgium
    For correspondence
    Damien.Hermand@unamur.be
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Danny Reinberg, Howard Hughes Medical Institute, New York University School of Medicine, United States

Version history

  1. Received: May 26, 2015
  2. Accepted: June 19, 2015
  3. Accepted Manuscript published: June 22, 2015 (version 1)
  4. Version of Record published: July 15, 2015 (version 2)

Copyright

© 2015, Materne et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,686
    views
  • 640
    downloads
  • 19
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Philippe Materne
  2. Jayamani Anandhakumar
  3. Valerie Migeot
  4. Ignacio Soriano
  5. Carlo Yague-Sanz
  6. Elena Hidalgo
  7. Carole Mignion
  8. Luis Quintales
  9. Francisco Antequera
  10. Damien Hermand
(2015)
Promoter nucleosome dynamics regulated by signaling through the CTD code
eLife 4:e09008.
https://doi.org/10.7554/eLife.09008

Share this article

https://doi.org/10.7554/eLife.09008

Further reading

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics
    Lisa Baumgartner, Jonathan J Ipsaro ... Julius Brennecke
    Research Advance

    Members of the diverse heterochromatin protein 1 (HP1) family play crucial roles in heterochromatin formation and maintenance. Despite the similar affinities of their chromodomains for di- and tri-methylated histone H3 lysine 9 (H3K9me2/3), different HP1 proteins exhibit distinct chromatin-binding patterns, likely due to interactions with various specificity factors. Previously, we showed that the chromatin-binding pattern of the HP1 protein Rhino, a crucial factor of the Drosophila PIWI-interacting RNA (piRNA) pathway, is largely defined by a DNA sequence-specific C2H2 zinc finger protein named Kipferl (Baumgartner et al., 2022). Here, we elucidate the molecular basis of the interaction between Rhino and its guidance factor Kipferl. Through phylogenetic analyses, structure prediction, and in vivo genetics, we identify a single amino acid change within Rhino’s chromodomain, G31D, that does not affect H3K9me2/3 binding but disrupts the interaction between Rhino and Kipferl. Flies carrying the rhinoG31D mutation phenocopy kipferl mutant flies, with Rhino redistributing from piRNA clusters to satellite repeats, causing pronounced changes in the ovarian piRNA profile of rhinoG31D flies. Thus, Rhino’s chromodomain functions as a dual-specificity module, facilitating interactions with both a histone mark and a DNA-binding protein.

    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression
    Ramona Weber, Chung-Te Chang
    Research Article

    Recent findings indicate that the translation elongation rate influences mRNA stability. One of the factors that has been implicated in this link between mRNA decay and translation speed is the yeast DEAD-box helicase Dhh1p. Here, we demonstrated that the human ortholog of Dhh1p, DDX6, triggers the deadenylation-dependent decay of inefficiently translated mRNAs in human cells. DDX6 interacts with the ribosome through the Phe-Asp-Phe (FDF) motif in its RecA2 domain. Furthermore, RecA2-mediated interactions and ATPase activity are both required for DDX6 to destabilize inefficiently translated mRNAs. Using ribosome profiling and RNA sequencing, we identified two classes of endogenous mRNAs that are regulated in a DDX6-dependent manner. The identified targets are either translationally regulated or regulated at the steady-state-level and either exhibit signatures of poor overall translation or of locally reduced ribosome translocation rates. Transferring the identified sequence stretches into a reporter mRNA caused translation- and DDX6-dependent degradation of the reporter mRNA. In summary, these results identify DDX6 as a crucial regulator of mRNA translation and decay triggered by slow ribosome movement and provide insights into the mechanism by which DDX6 destabilizes inefficiently translated mRNAs.